Stanford University is home to some of the world's most progressive biological and medical research. Proteomics as a research application, providing insightful answers to fundamental biological questions, is now a prerequisite. One of the cornerstones of proteomics, if not the foundation, is mass spectrometry. The technological development of mass spectrometric instrumentation in parallel with computational resources over the past five years has given rise to the complete identification and quantification of the yeast proteome, complete post-translational mapping of human histones and isoforms thereof, as well as the ability to map signaling events (phosphoproteome) as a response to stimulation on a global proteomic scale. These profound findings are inextricably linked to the capabilities of modern instrumentation. This proposal seeks funds to assist in the purchase of a new LTQ Orbitrap XL ETD mass spectrometer. The Orbitrap will be professionally operated and maintained in Stanford's mass spectrometry core facility, Stanford University Mass Spectrometry (SUMS). SUMS'current 1-year user base includes 245 students, faculty, and staff in 80 research groups from 26 departments distributed across the schools of Medicine (60%), Humanities and Sciences (30%), and Engineering (10%). The capabilities of the Orbitrap mass spectrometer are proven, and the technical expertise to operate the instrumentation and translate the resulting data into biologically meaningful results is already present in SUMS. The addition of the Orbitrap would make research projects that are now in high demand viable. Amongst many other applications, the high mass accuracy and sensitivity of the instrument would enable quantitative proteomic studies on cancer cells, stem cells, and fetal mouse serum. The capabilities of ETD would be utilized in phosphoproteomic characterization of proteins involved in plant cell signaling and tumorgenesis. In addition, the instrumentation would enable top-down and middle-down characterization of proteins critical to viral progression. The research projects of seven major users, as described in the proposal, are highly relevant to human health and disease, with particular impacts on viral and bacterial infections, stem cells and cell fate, and several types of cancers. These projects are representative of the types of challenges faced by many researchers on campus. PUBLIC HEALTH RELEVANCE: Proteomics is the study of proteins on the broadest scale, determining the most basic information about proteins: the what, who, where and why have implications in understanding disease and disease states. Mass spectrometry is one tool which has addressed and will continue to answer these questions definitively. Applying the proven capabilities of the LTQ Orbitrap XL ETD mass spectrometer to the research described in this proposal has potential to impact human health and disease, moving research forward in numerous areas, including viral and bacterial infections, stem cells and cell fate, as well as several types of cancers.